This subproject is one of many research subprojects utilizing the resources provided by a Center grant funded by NIH/NCRR. The subproject and investigator (PI) may have received primary funding from another NIH source, and thus could be represented in other CRISP entries. The institution listed is for the Center, which is not necessarily the institution for the investigator. Ultrasound study of brachial artery flow-mediated dilation is emerging as a commonly used test for investigation of endothelial function, specifically risk for coronary artery disease. In children, femoral artery flow mediated dilation has been used to identify abnormalities in children with familial dyslipidemia and brachial artery flow in children with Kawasaki Syndrome. We hypothesize femoral and/or brachial artery flow mediated dilation may be useful in identifying abnormalities in flow mediated dilation in HIV infected children and may correlate with the observed abnormalities in cholesterol and triglycerides now commonly observed in HIV infected children treated with protease inhibitors. The vascular endothelium plays a central role in the regulation of vascular homeostasis by releasing paracrine factors that influence vascular tone, blood fluidity, and inflammation. A prototypical and relevant endothelial product is nitric oxide (NO), which is a vasodilator and an inhibitor of platelet activity, leukocyte adhesion, and smooth muscle cell proliferation. NO is synthesized from the amino acid L-arginine by the enzyme nitric oxide synthase (eNOS), which established that endothelium-dependent flow-mediated dilation (FMD) is dependent on nitric oxide production and that this response can be detected in the brachial or femoral artery using the non-invasive methodology proposed for the present study. Loss of the biologic activity of endothelium-derived NO is important in both the early and later stages of atherosclerosis. The clinical relevance of endothelial dysfunction has been established in adults by demonstrating a link between endothelial dysfunction and cardiac events. In children, high resolution ultrasound of the femoral or brachial artery has been used to measure changes in arterial diameter in response to reactive hyperemia and to glycertrinitrite. Flow increase is induced by deflation of a blood pressure cuff placed around the thigh distal to the femoral artery or deflation of a blood pressure cuff placed around the upper arm. The cuff is released after 3-5 minutes and the artery scanned continuously from 30 seconds before to 90 seconds after deflations. Ten minutes later, a second resting scan is recorded. Changes in diameter of 0.1-0.2 mm can be detected accurately (Sorensen KE, et al. Impairment of endothelial-dependent dilatation is an early even in children with Familial Hypercholesterolemia and is related to the lipoprotein 9a) (Level. J. Clin. Invest. 1994;93:50-55).
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